CHAPTER IV

THE FLUIDS OF THE BODY

From one-fourth to one-third of the whole body is fluid. If the skin be regarded as a water-tight bag, three-fourths or rather less of its contents are solid, one-fourth liquid; and even its apparently solid contents, the tissues, contain much water. Water is an essential constituent of protoplasm. It is also present in cell-juice. The estimate given above does not include the fluid within the cells, but only the fluid with which the cells are bathed. In a general sense this extracellular fluid, excluding blood, is termed =lymph=. It occupies the spaces of a gauzy “connective tissue,” which connects, or separates—the terms are equally appropriate—muscles, nerves, glands, and other tissues of specialized function. Nowhere, except, in a fashion, in the spleen, does blood come in contact with a cell. The lymph which more or less surrounds them is the bath from which cells receive their food and oxygen, into which they excrete carbonic acid and tissue-waste. The network of lymph-spaces is traversed by capillary bloodvessels with walls composed of flattened connective-tissue cells. Such cells are usually spoken of as elements of an “endothelium.” As the epithelium covers the surface of the body, so endothelium lines its cavities. Endothelial cells are thin scales or tiles with sinuous borders dovetailed one into another. That the tiles which form the walls of capillary vessels are not cemented together in any proper sense is shown by the facility with which white blood-corpuscles, leucocytes, by their amœboid movements, push them asunder when making their way from the blood-stream into the tissue-spaces, or _vice versa_. They offer no more resistance to a leucocyte than a pair of curtains hanging in front of a door offers to a child. Yet so long as the endothelial cells are alive they keep their edges in such close apposition as to constitute a continuous membrane which shuts off blood from lymph. They are always close enough together to prevent red blood-corpuscles from escaping from the capillary vessels; but their resistance to the passage of the different constituents of plasma varies greatly. The membrane which they compose is more complete and less pervious, or less complete and more pervious, in accordance with the nature of the tissues which surround it, and their varying needs. The blood-passages of the liver may be described as filters. The escape of red blood-corpuscles into lymphatic vessels is prevented, but they offer practically no resistance to the plasma. Plasma—“lymph,” as it is termed as soon as it is outside bloodvessels—passes through the walls of the capillaries of the liver unchanged in constitution. Where they traverse glands (other than the liver), muscles, skin, and various other structures, the walls of capillary vessels, while offering practically no resistance to water and diffusible salts which can pass through membranes, prevent proteid substances from passing from blood to lymph, except in extremely small quantities. In this way an exquisite balance is automatically maintained. Water and salts pass out as they are needed. But they never pass out in excess, because the protein-containing blood-stream tends to keep them in, in virtue of the same attractive force which enables it to suck in the oxidized products thrown into the lymph by the tissues. Whatever a tissue needs it takes from the lymph. Suppose that bone is being formed. Large quantities of lime and phosphates are needed for the calcification of the cartilage in which it is modelled. The cartilage absorbs lime and phosphates from the lymph which bathes it. Lime salts and phosphates immediately begin to diffuse from blood into lymph. The hurrying blood-stream brings up further supplies from the walls of the intestine, products of digested milk and other foods. Lymph contains (although not in the same proportions) everything which blood contains. Many an analogy may be found in the world of economics, although no illustration would be sufficiently complete. From the lymph tissues take the fuel that they need, the oxygen with which to burn it, the foods for their own repair, the raw materials for their arts. Into it they throw their smoke, their drainage, the slag and refuse of their factories. The blood replaces the supplies as they disappear. It absorbs all waste. Lymph occupies streets, market-place, passages, corridors. The blood-stream is a closed system, rolling down the streets and through the market-place, on its never-ceasing circuit from port and mine to open air and open sea. From the alimentary canal it picks up food and fuel; the lungs give it oxygen, and disperse its carbonic acid; the kidneys purge it of non-gaseous waste.

The facility with which the constituents of blood pass out to the lymph, and the constituents of lymph pass into the blood, depends upon the condition of the walls of the capillary vessels. Water and substances dissolved in water might pass through the wall of a capillary vessel in either of three ways—by filtration, by osmosis, or by secretion. A filter is a porous barrier, which allows water and all substances dissolved in water to traverse it. The solution passes through unchanged in composition. Only solid particles are kept back. The rapidity with which fluid passes through a filter varies as the difference between the pressure on the one side and the pressure on the other. A membrane does not allow of filtration. Water and things dissolved in water pass through it by osmosis. Some things it will not allow to pass; such, for example, as gum, mucin, white of egg. To others it offers resistance in varying degrees. Most of the things that can diffuse through a membrane are capable of crystallization; but the membrane exercises some control over the passage of even crystallizable substances when in solution. If a membranous tube containing water in which proteins, sugar, and various salts are dissolved is hung in a basin of pure water, the proteins remain in the tube; the sugar and the salts pass through its wall into the surrounding water. But they pass at different rates. Those of small molecular weight pass more quickly than those whose molecule is heavy. After a time a condition of equilibrium is established. No more salts pass out of the tube. If now the contents of the tube and the contents of the basin are analysed, it will be found that the tube contains all the proteins, some of the sugar, and some of each of the salts, although not in the proportions in which they were present at the commencement of the experiment. The water in the basin contains some sugar and some of each of the salts, but not in the same proportions in which they are found in the tube. As a matter of fact, the same number of molecules would be present, per unit volume, on each side of the membrane—in the tube and in the basin. In this respect the percentage composition of the two solutions would be the same. But some of the molecules being heavy, others light, the weight of salts which unit volume of the solution in the tube would contain would not be the same as the weight of salts in unit volume of the solution in the basin. A membrane exerts a discriminating action on the substances which pass through it. Secretion is osmosis in disguise. It may be even filtration in disguise. A gland-cell (like an amœba) takes things up and passes them out without regard to their osmotic equivalent. It seems to exercise a choice. It seems to act in disregard of the laws both of filtration and of osmosis. So, at least, it appears to us when we are looking at the result in ignorance of what has happened inside the living cell. The passage from blood to lymph and _vice versa_ through the wall of a capillary vessel is in certain situations or at certain times a mere process of filtration; at others a process of restricted filtration. If the wall is behaving as a perfect membrane, it is a process of diffusion, or osmosis. It seems unnecessary to regard it, in any case, as a process of secretion. The more widely the capillaries are dilated, the less resistance do they offer to exudation. The narrower their calibre, the greater is the restraint which they place on the escape or entrance of fluid. When the skin of the palm of the hand is not sufficiently thick to protect the soft tissues beneath it from the injurious effects of the prolonged pressure of an oar or an axe, the capillary vessels of the under-skin dilate; more lymph transudes; the skin is raised up as a blister. The same thing happens when the capillaries are dilated and paralyzed by scalding water. The fluid of a blister has much the same constitution as blood-plasm, except that it contains less proteid substance. These results might be regarded as purely mechanical—the direct effects of pressure or heat upon the membranous capillary wall. But the “vital” element is more important. The capacity of endothelium to act as a barrier depends upon its nutritive condition—its vital integrity, as it might be termed; which no doubt in the last resort means its chemical relation to the fluids which bathe it. Now and again blebs, like blisters, are formed on the skin—the herpes which appears about the mouth; urticaria, which is more generally distributed; and various other cutaneous disorders. Frequently a connection can be traced between these eruptions and the consumption of a particular food. An attack of urticaria results not uncommonly from eating lobster, mussels, rook-pie, or some few other articles of diet. Various things—bad fish, for example—may produce the same effect; but shell-fish have an especially evil reputation. If extract of lobster or of mussels be injected into the blood of an animal, the amount of lymph which leaves the blood is markedly increased. The extract acts as a poison upon the endothelium of the capillary walls. It increases its permeability in all conditions in which lymph escapes in undue quantity from the blood-stream, or escapes more rapidly than it is absorbed; the nutritive condition of the endothelium is disturbed. Its unusual permeability is due in part, no doubt, to the dilatation of the capillary tube, the stretching of its membranous wall; but it is due also to the diminished vigour of the endothelial cells. They have lost to a certain extent their capacity for holding their edges in perfect apposition.

When the circulation is sluggish, owing to the inefficiency of the heart, the tissues become œdematous. In other words, lymph accumulates in the tissue-spaces. When the skin of a healthy person is pressed, it returns to its natural position as soon as the pressure is removed. If there is a tendency to dropsy—for ages the term “hydropsia” has been thus familiarly clipped—the finger leaves a pit behind it when pressed upon the skin. It is some little time before the lymph in the connective-tissue sponge readjusts the surface. Excessive escape of lymph from the blood, or its insufficient return into the blood, may also be the result of obstruction to the flow in the great veins. When the veins of the leg are varicose, the weight of the column of blood in the distended vessels impedes its circulation. After standing, the tissues about the ankle become œdematous. The œdema disappears on lying down. A hardening (cirrhosis) of the liver impedes the circulation of the blood which comes to it through the portal vein from the walls of the alimentary canal. The capillaries of the stomach and intestine are distended. Lymph accumulates in the abdominal cavity, producing ascites, another form of dropsy.

It is almost hopeless to attempt to disentangle the various factors which disturb the balance between blood and lymph—excessive outflow from blood, deficient inflow from lymph, stretching of the endothelium of the capillary tubes, imperfect nutrition and consequent imperfect apposition of the endothelial scales, increased permeability of the scales. The exudation which accompanies inflammation would seem to be due to the diminished vitality of the endothelium rather than to a mechanical factor, such as increased blood-pressure in the capillaries, and their consequent distention. Ascites is, apparently, a purely mechanical result of the resistance offered to the passage of blood through the liver; but pleurisy, the accumulation of lymph in the space between the lungs and the chest-wall, cannot be explained in the same way. There is no undue pressure on the vessels in which the blood circulates through the inflamed pleura (the investing membrane of the lungs and lining membrane of the chest), yet the walls of the capillaries fail to maintain a proper balance between blood and lymph.

Hitherto we have spoken of the lymphatic system as a labyrinth of communicating spaces containing stagnant fluid, which is kept in a fitting state by egress and ingress out of and into blood. Such a mental picture is substantially correct. But the system is complicated by the presence of lymphatic vessels. Cells of the connective-tissue sponge-work arrange themselves side by side. They flatten into endothelial scales. The borders of the scales close up. They form lymphatic channels, wider than blood-capillaries, but strictly comparable in every other respect. The lymph capillaries unite into larger vessels. The larger vessels are connected by cross-branches; they form plexuses. Their walls are strengthened with fibrous tissue. Like the veins, they are abundantly provided with valves, which check any tendency to a backward flow on the part of the fluid which they contain. Lymphatic plexuses surround and accompany the larger bloodvessels. They are disposed on the surface of muscles and glandular tissues. They are abundant beneath the skin. Nearly three centuries ago the lymphatic vessels of the mesentery, which collect products of digestion, especially fat, from the walls of the alimentary canal, were recognized owing to the milkiness of their contents after a meal. They were, on this account, termed “lacteals.” Other lymphatic vessels, owing to their transparent walls and colourless contents, are not easily seen; but they are readily injected with mercury or other fluids which render them conspicuous. In the upper part of the thigh, in the armpit, or in the neck, they are about large enough to admit a crow-quill. Those from the lower limbs, from the viscera, and from the walls of the abdomen converge to a receptacle which lies in front of the spinal column. The receptaculum chyli is continued upwards as the thoracic duct, which pours the lymph into the great veins of the left side of the neck and of the left arm just where they join together.

The thoracic duct provides for the overflow of lymph from the spaces of the body. There is no circulation of lymph. Lymph from the liver and from the intestines is constantly draining into the thoracic duct, and thus returning to the blood-stream by a short direct route, entering it without the necessity for reabsorption through the walls of capillary vessels. By no means all of this fluid has exuded from the blood-stream. Much of it is water which was poured into the stomach as gastric juice, and into the intestines as the secretions of the pancreas and other glands, or imbibed through the mouth and absorbed by the lymphatics of the alimentary canal. The remainder of the water taken up from the alimentary canal enters its bloodvessels. The diluted blood flows to the liver, loaded with digested products which the liver will store. As the blood parts with them the additional water which has served for their transport exudes from the capillaries of the liver into lymphatics, which empty it into the thoracic duct. Large quantities of water are used in washing out digested products. Secreted into the alimentary canal by the digestive glands, it passes out through its wall as the vehicle of digested products. Collected by lymphatic vessels, it is either carried directly into the thoracic duct, or passed from lymph into blood, carried by blood to the liver, again transferred from blood to lymph, and borne by the lymphatic vessels of the liver to the thoracic duct.

Water exuded from blood into lymph may be reabsorbed into the blood near the place where it was poured out, or it may reach the blood via the thoracic duct. It would seem that the former is the natural, the latter the emergency route; the former the course taken when an organ is tranquil, the latter a necessity when the organ is active. If the large lymphatic vessels of a limb are cut, no lymph escapes from them so long as the limb is at rest. When the muscles contract lymph begins to flow. If the limb is flexed and extended by hand, lymph flows. If the muscles are squeezed or massaged, lymph flows. As the flow is set up both by active contraction of the muscles and by passive movements in which the muscles do not take part, it clearly must be due to external pressure on the lymphatic vessels. As they are provided with valves, squeezing them converts them into pumps. The fluid which they contain is bound to go forwards. Additional fluid is squeezed into them from the tissue-spaces. To a large extent, therefore, the outflow of lymph from contracting muscles is to be explained as the result of the pressure which the swelling muscles exert upon the lymphatic vessels within their sheaths. But there is another factor which must not be overlooked, although it cannot readily be estimated. When a muscle is actively contracting its bloodvessels dilate. There is a greater exudation of lymph; and reabsorption by blood is not equal to the exudation. The surplus leaves the limb by the lymphatic vessels. A gland is never at rest. In the intervals between the ejection of its secretion its cells are preparing materials for the next outflow. Lymph is always flowing from a gland; its amount increases as the activity of the gland increases. More lymph leaves the blood when the gland is exceptionally active than when it is relatively quiet. Some of it is not reabsorbed into the blood. A certain proportion of the waste products of the active gland are hurried away by the overflow system in the direction of the thoracic duct.

Lymph is the reservoir of nutriment upon which every cell in the body draws. It is improbable that in health and under normal conditions the activity of any organ is ever restricted for want of sufficient food. As food is removed from lymph, it is instantly replaced by fresh food from the blood. There is some evidence—not very clear—that the removal of waste products offers greater difficulty than the renewal of supplies of food. When the activity of muscles has been excessively prolonged they ache. It has been supposed that their unwillingness to do more work is due, not to the exhaustion of the food which they use up when contracting, but to the inadequacy of the lymph and blood to carry off all refuse. This, at least, is the explanation of fatigue which is usually offered, although it is difficult to understand why the arrangements for removing waste products which have worked to perfection for eight hours should during the ninth hour become rapidly ineffective.

If a frog’s muscle, cut out of the body, has been made to contract until it refuses to work any longer, it again responds to stimulation after a solution of salt has been passed through its bloodvessels. The salt-solution brings no food; the only thing it can do is to wash away waste products. But this experiment upon a tired, isolated muscle does not necessarily throw light upon the nature of fatigue in muscles under normal conditions. The isolated muscle is using up, in contracting, food which it has stored. Cut off from the circulation, it has no means of getting rid of the lactic acid and other products into which food is changed. They may well have accumulated to a poisonous extent long before all the food has been used up. Hardly more cogent is the argument based upon the benefit which a tired man experiences from hot baths, massage, and the like. They take away the feeling of tiredness, but it does not follow that this result is due to the removal of waste products. Quickening the circulation of blood brings about renewal of the lymph. Renewal of lymph means fresh supplies of food as well as removal of waste products. Even human muscles are not perfect as machines. They will not work for an unlimited spell. There comes a time when they must have rest. Something goes wrong in the admirable adjustment which has hitherto provided exactly the right amount of food and exactly the necessary freedom from the products of action. A feeling of fatigue is the signal that the apparatus is not in a condition to work longer; but whether this feeling is due to a dislocation of the balance of supply and loss, or to some deterioration of the apparatus which calls for rest and renovation, it is at present impossible to say. It is not due to the exhaustion of muscle food. A more powerful stimulus, the urgency of fright or some other strong emotion, or an electric current applied directly to the muscle or its nerve, will still induce vigorous contraction. The muscles of a hare that has been coursed until it can run no farther still contain glycogen, muscle food.

Glycogen is stored in the liver. Fat, if it is assimilated in excess of the needs of the body, accumulates in the connective tissues. Proteins, if in excess, are either destroyed by oxidation, or partly destroyed and partly converted into fat. Increasing the amount and richness of the food does not, if nutrition is already at its best, improve the quality of the blood. The surplus of food is either stored or burnt. The composition of lymph is unaffected. Its quality is not improved by taking more food than enough. A perfect balance is maintained. Every cell is able, when conditions are normal, to obtain as much nutriment as it needs. It cannot get more. It cannot lay by food and shirk work. If it did it would grow. Reaching its optimum size, it would divide. Additional tissue would be formed. But when it does more work it needs more food; and it is a matter of common experience that the system is so adjusted that food is supplied to the tissues, not reluctantly, but with a slight tendency towards generosity. Working harder than usual, they find the lymph by which they are bathed somewhat richer in the materials that they need than the necessities of the case demand. They are able not merely to obtain all they want, but a little more. Activity favours growth.

Many attempts have been made to show that if a part of the body has more than its share of food it grows to an excessive size. John Hunter grafted a cock’s spur into its comb. It grew to monstrous dimensions. Such a result favours the view, but it is not quite conclusive. Undoubtedly the comb was richly supplied with blood, but it does not follow that the cells of the spur were able in their new situation to take advantage of this supply. Besides, the spur when projecting from the head was not subject to the accidents to which it was exposed whilst on the leg. Its size was not kept down by friction. Nor was it as hard and compact as it would have been in its normal situation. It is scarcely possible to devise any experiment that would be satisfactory now that the relations between blood and lymph and lymph and tissues are understood. In certain pathological conditions, however, hypertrophy is the result of the hyperæmia of chronic inflammation; and there is little doubt that, if we could arrange for a certain group of cells to receive lymph richer in food and freer from waste products than the perfect adjustment of supply to needs normally allows, the cells would grow.

Under perfectly healthy normal conditions growth can be induced only by use. Nature supplies the fuel which is used during activity, and a balance of food available for the construction of additional machinery. The muscle which is called upon to do work develops a greater capacity for work.

When nutrition is not at its best, the growth of muscle may be favoured by external pressure which squeezes lymph out of its tissue-spaces, and therefore leads to increased exudation from the blood. It is not improbable that in badly nourished tissues the circulation of blood is somewhat torpid and the lymph stagnant. A feeble circulation usually results in some œdema. The muscles, or rather the connective tissue which envelops and penetrates them, feels doughy, instead of being, as it should be, firm and elastic. Under these conditions massage is undoubtedly of service. Squeezing the muscles displaces lymph, and, if the pressure is properly directed, drives it along the lymphatic vessels. Fresh lymph exudes from the capillary bloodvessels, and the muscle-fibres, surrounded with a more abundant supply of nutriment, benefit, as, in a vigorous person, they benefit from use.

Lymph is an exudate from blood. Its composition therefore depends upon that of blood-plasma, but it tends to differ from it owing to the influence of two causes. In the first place, the walls of the capillary bloodvessels restrict exudation. Red blood-corpuscles cannot pass through them. Proteins which are non-diffusible are, according to the circumstances of the tissues, held back to a greater or to a less extent. The pseudo-capillaries of the liver let them pass, as has already been said. The capillaries of the limbs restrict their passage to such proportions as, it may be supposed, are absolutely necessary for the nutrition of the tissues. In the second place, tissues remove food from lymph and add to it waste products. Hence the lymph issuing from a limb, after full contact with the tissues, contains less of the former and more of the latter—less sugar, for example, and rather more oxidized nitrogenous substances, lecithin and other things termed collectively “extractives,” because they can be extracted from dried blood or lymph by ether. The reaction of lymph is alkaline. After a time it coagulates, but coagulation is slower, and the clot less firm than in the case of blood.

As the composition of lymph depends upon the source from which, and the conditions under which, it has been obtained, it is unnecessary to state the results of a chemical analysis. It suffices to say that lymph contains all the substances which are present in the plasma of blood, but not necessarily in the same total amount or in the same relative proportions. Speaking generally, leucocytes are present in about the same numbers as in blood—6,000 to 8,000 to the cubic centimetre; but leucocytes are everywhere present: in blood, in the lymph, in lymph-vessels, in the tissue-spaces. As they are not passively floating bodies like red blood-corpuscles, but active migratory organisms, they tend to accumulate in one situation and withdraw from another, in accordance with the opportunities which the different localities afford. They desert effused lymph, blisters, ascitic fluid, and the like. They are not found in the lymph in the pericardium. There are fewer in the lymph coming from the intestines after a meal than in the same lymph during the intervals between meals. Their departure from effused lymph might easily be explained. It is not so easy to account for their comparative absence from the lymph in the lacteals when it is heavily charged with fat and other products of digestion. Such leucocytes as are present at this time are loaded with fat granules which they have stolen from the chyle, as the lymph in the lacteals is usually termed. One would need to be very intimate with a leucocyte before one ventured to give reasons for all its movements. Lymph contains the same proteid substances as blood, and in the same relative proportions, but usually in smaller quantity.

Incidental reference has been made to the great lymph-spaces—peritoneal, pleural, and pericardial. The brain and spinal cord are separated from their outer membranes by a lymph-space. There are also spaces within the brain—the ventricles—and a central canal in the spinal cord. The aqueous and vitreous humours of the eye are also lymph-spaces, although the latter contains some remnants of tissue. The joint cavities are lymph-spaces. So also are the bursæ which surround tendons or separate them from bones. It is not, however, justifiable to include all these cavities in a single category, either from the point of view of their purpose, their mode of formation, or the nature of their contents. The peritoneal, pleural, and pericardial spaces are parts of the great primitive body-cavity, or cœlom. The two first are potential rather than actual. Normally they contain just sufficient fluid to moisten the apposed surfaces of the endothelium which lines their walls and covers the organs which they contain. There is no fluid in them which can be collected and labelled “peritoneal” or “pleural” fluid. The purpose of the spaces is to allow of movement without friction—in the one case of the intestines, in the other of the lungs. It is possible to take a spoonful or so of fluid out of the space which surrounds the heart. It has the usual composition of lymph. It contains proteins, but is not spontaneously coagulable. Leucocytes are absent, a fact which probably accounts for its not clotting. The fluid inside the cerebro-spinal system is extremely dilute. Its principal salt—its principal constituent, indeed—is sodic chloride. It contains hardly a trace of proteins, and these in a modified condition—proteoses. It also contains pyro-catechin, a benzoic alcohol. This substance has long been recognized as a constituent of cerebro-spinal fluid, owing to the fact that, like sugar, it reduces copper salts when heated with them in an alkaline solution. It appears to be one of the products of proteid decomposition. Although exuded as lymph from the bloodvessels of the chorioid plexuses, the composition of cerebro-spinal fluid has been profoundly changed by the activity—it might almost be called the digestive activity—of the epithelium which lines the cerebro-spinal canal. There is a theory that the ancestors of all vertebrate animals were organized on a very different plan from that of their distant descendants. Our cerebro-spinal canal was their stomach and intestine. It would appear that the lining epithelium of these organs, although disused for millions of years, cannot resist the temptation to digest the lymph which they contain! The fluid in joints contains mucin (the essential constituent of mucus), or a substance resembling mucin. In this case the joint-membrane has added something to lymph without removing or destroying any of its other constituents.

Other illustrations might be given showing how the plasma of blood is altered in composition while it is passing out of, or after it has passed out of, capillary bloodvessels. Perhaps it would be more logical to start on the outer side of the walls of the capillaries; since blood may, very properly, be regarded as a tissue, dependent, like all other tissues, upon diffusion from lymph for the nutrient materials that it needs. In the wall of the alimentary canal it receives supplies _via_ the lymph. It drops them in the liver, its _garde-manger_, to pick them up again as they are wanted. The torrent of lymph which the thoracic duct discharges into the veins of the neck conveys the fat which could not traverse the walls of the capillary bloodvessels, and much of the reserve of food which the blood had deposited in the liver. Only about one-quarter of the fluid of the body (one-thirteenth of the body-weight) is included within the blood-system; but this enclosed fluid, owing to the fact that it is kept in circulation by the heart, replenishes and purifies the much larger quantity which does not circulate. The unenclosed lymph has in particular situations a chemical composition which varies widely from that of the blood. Imagine a marsh through which a river flows—the vast plains of water-plants on the Nile above Fashoda, for example. There is a constant interchange between the flowing water of the river and the stagnant water of the marsh. In any given part of the marsh the quality of the water will depend upon what it has been able to take from, and what it has given back to, the river; upon what the water-plants have taken from it, and what they have added to it. Boats which cannot penetrate the walls of reed keep to the open channel of the Nile. Fish swim, now in the river, now in the narrow passages and open pools of the marsh. So it is, in a way, with the fluid in the spaces and cavities of the lymphatic system and in the bloodvessels which traverse them, and with its migratory inhabitants. In our extravagant analogy read leucocytes for fish. Fish have two reasons for wandering from river to marsh. Amongst the water-weeds they hunt for food; they seek quiet places in which to breed. In this matter the analogy holds good. A leucocyte may be overtaken with cell division anywhere—in the blood-stream or in a lymph-vessel. But cell division very rarely occurs except in certain favoured spots. The breeding-places chosen by leucocytes are sheltered situations in connective tissue where the blood-supply is abundant, and the eligibility of such a spot is much increased by its being near to a field where their services are likely to be called for. The nests of connective tissue made by the leucocytes are of three kinds, termed respectively diffuse adenoid tissue, lymph-follicles, and lymphatic glands. The connective tissue beneath the mucous membrane of the whole of the respiratory tract—trachea, bronchi, and bronchioles—is diffuse adenoid tissue. It presents no special structure, but its spaces are packed with leucocytes in various stages of cell division, and young leucocytes, or lymphocytes, as they are usually named. Some of the lymphocytes make their way into the blood or into the lymph. Others, acquiring their full dimensions, scour the epithelium which lines the respiratory tract for germs and other foreign bodies which are drawn into the tract with inspired air. They may be seen pushing aside the cells of the lower strata of the epithelium, on their way to the surface, or returning to the subepithelial connective tissue with germs, or particles of soot, or débris of epithelial cells which they have taken into their substance (Fig. 4, B).

The tonsils are examples of follicular lymphoid structures. They lie one on either side of the entrance to the gullet, between the two folds (the anterior and posterior pillars of the fauces) by which the soft palate is continued to the side of the tongue. Normally the tonsil is not visible, but when inflamed it may project sufficiently to be seen; and its surface may then be covered with mucus and pus. It is liable to become enlarged in childhood, owing to chronic inflammation. A section of the tonsil shows it to consist of clusters of lymph-follicles lying beneath the mucous membrane. The term “follicle” is unfortunate. It conveys no idea of the form or structure of one of these masses of lymph-cells; and it is, besides, applied to things of an entirely different character—for example, the pits of mucous membrane which sink down between the masses of lymphoid tissue in the tonsil. The expression “follicular tonsillitis” does not refer to the lymph-follicles, but to the epithelial pits. It is a condition in which a drop of pus is to be seen in the mouth of each of the pits. A lymph-follicle is a small rounded clump of connective tissue, denser on its periphery than in its centre. Its bloodvessels are disposed chiefly on the periphery. Lymphatic streamlets arise in the centre. Its outer portion is closely packed with dividing lymph-cells and young leucocytes, which as fast as they are formed migrate towards the centre, and eventually escape from the follicle by the lymphatic vessels. The connective tissue which invests and separates the follicles is full of leucocytes. Removal of the tonsils is followed by no ill effects. They are not essential to our well-being. Nevertheless, they have important functions to perform. They are barracks crowded with leucocytes, which guard the pass into the alimentary canal. Their leucocytes incessantly patrol the mucous membrane, capturing germs, removing fragments of injured epithelium, striving to make good the mischief to which this part of the alimentary canal is peculiarly liable. The enlargement of the tonsil which results from frequent sore throat is a response to the demand for an increase in the supply of these little scavengers, in order that they may cope, not only with objectionable things outside the walls, but with the still more pernicious germs which during an attack of sore throat succeed in breaking through the epithelium. It is the invaders which elude the vigilance of the leucocytes that cause fever and other general symptoms. Other notable groups of lymph-follicles are found in the middle portion of the small intestine, where they form oval patches, about three-quarters of an inch long by half an inch broad—Peyer’s patches. The leucocytes which are developed in them search the walls of the intestine for germs. During an attack of enteric fever the patches become inflamed, and one of the greatest risks which the patient runs is the risk of ulceration of a patch and the perforation of the intestinal wall.

The abundant provision for the multiplication of leucocytes shows that the destruction of these cells must occur on an equally large scale. Every day large numbers die. Where this occurs, and how their dead bodies are removed, is not certainly known. Doubtless they are eaten by their fellows, their substance oxidized, and the products—carbonic acid, water, and nitrogenous waste—thrown into the lymph. There is some reason for thinking that a part of the nitrogenous waste is excreted in the form of uric acid (_cf._ p. 216). The daily production, and consequent destruction, of leucocytes shows that their metabolism is a factor which cannot be overlooked when we are making up the body’s accounts.

The fixed tissues receive their nutriment in a digested condition. Leucocytes digest it for themselves. In many cases, although not in all, the cells of fixed tissues last throughout life, so far as their outer form is concerned, although their molecules are oxidized and replaced by new material. It is not improbable, therefore, that there is a difference between the metabolism of the fixed tissues and the metabolism of leucocytes. The whole of a wandering cell, its nucleus included, breaks down and has to be removed. We do not know that this occurs in the case of a fixed cell. On the strength of evidence which points, apparently, to a chemical relationship between nuclear substances and uric acid, it has been inferred that the two chief nitrogenous products which are excreted by the kidney are divisible into the one which in the main represents the oxidation of fixed cells, urea, and the other, uric acid, largely derived from the oxidation of wandering cells.

The valiant leucocytes do their best to cope with all the rubbish, whether living or dead, that needs removal. They flock to any situation in which germs are numerous or tissue has been destroyed. If all goes well they take the foreign matter into their substance—dead tissue is matter foreign to the body—and either digest it in the course of their ordinary progress, or retreat with it, if they cannot digest it, to the nearest lymphatic gland. But in their efforts to reach objectionable matter they are apt to wander too far from the healthy lymph from which they obtain oxygen for their own respiration. Unable to breathe, they die. They lose the power of extruding pseudopodia. Their extensible, prehensile processes are drawn in. Assuming a globular form, they float helplessly in what once was lymph. Their body-proteins are largely changed to fat. As “pus cells,” they are thrown off in the discharge from an ulcer, or accumulate in the cavity of an abscess. A pus cell is a dead and fattily degenerated leucocyte.

The third kind of breeding-place of leucocytes, a lymphatic gland, has a more elaborate structure than the tissues with which we have already dealt. Lymphatic glands are about the size of beans, and of the same shape. They are found in the course of lymphatic vessels in situations where they are not exposed to pressure, such as the back of the knee, the groin, the front of the elbow, the armpit, in the neck above the collar-bone, and on either side of the sterno-mastoid muscle, behind the angle of the jaw. There are a number in the abdomen and in the thorax. Each lymphatic gland is invested by a strong fibrous capsule. Its artery enters, and its vein and efferent lymphatics leave, the concave side (the hilus) of the gland. The lymphatic vessels which bring lymph to it pierce the capsule on its convex side. It is divisible into two parts: (1) The adenoid tissue which surrounds the artery and its branches; (2) the open network of “lymph-ways” which invest this adenoid tissue. Leucocytes divide in the adenoid tissue. The young lymphocytes drop out into the lymph-ways. As a stream of lymph, brought by the afferent vessels, is always flowing into the lymph-ways, and out by the efferent vessel or vessels, the lymphocytes are carried with it towards the thoracic duct. A lymphatic gland is therefore an organ for adding leucocytes to lymph in the course of the lymph-stream. It has, however, another and equally important function. Leucocytes which have picked up germs or other foreign matter pass on with the lymph to a lymphatic gland. After entering its lymph-ways they leave the lymph-stream, squeeze into the adenoid tissue of the gland, and there come to rest with their burden. They remain in the gland until the foreign matter is digested, or, if it be indigestible, until they undergo dissolution, when the particles of soot or pigment are deposited from their débris in a harmless state. When the skin is tattooed, much of the Indian ink and other pigment remains where it was inserted with the needle, but some of it is picked up by leucocytes and carried to the nearest lymphatic gland.

Lymphatic glands are barriers which stop the spread of infection. They are the stations to which our police carry captured germs. The skin of the heel is abraded. Germs from the soil, or elsewhere, which have accumulated in a dirty stocking—owing to the warm moisture enclosed by an impervious boot, the woollen covering of the foot is a peculiarly healthy place for germs—enter the opened lymph-spaces of the subcutaneous tissues. Leucocytes hasten to the spot. They seize the invaders with their pseudopodia, engulf them in their body-substance, enter lymphatic vessels, and are rolled away by the lymph-stream. The instinct which brings them in ever-increasing numbers to the breach in the protecting skin can be explained only in terms of force. From our own conscious action to the causes which determine the movements of a leucocyte, or of an amœba, is so deep a drop that we prefer to recognize in the latter a merely chemical attractive force. “Chemiotaxis” we term the influence which draws leucocytes to the place where food is abundant; although it is also the place, one must admit, where in the interests of the body as a whole they run great risk of asphyxiation. It is appetite which draws a schoolboy to a bun-shop; a sense of duty prompts a fireman to risk his life in a chamber filled with smoke. We have no desire to humanize a leucocyte; but it is difficult to emphasize too strongly its independence. It would be absurd to use terms which imply that a leucocyte has a self-directive power; yet it is equally misleading to describe its migration to the seat of injury, its retreat with ingested germs to a lymphatic gland, its wriggling from the lymph-ways of the gland into the shelter of its adenoid tissue, in terms which imply that the forces which direct it are known, and their mode of action understood. The success which attends the inroads of germs is due to their amazing capacity for multiplication when they reach lymph or blood. It is useless to attempt to form an idea of the rapidity with which they divide, since we have no data upon which to base calculations. If the leucocytes fail to deal with the first few that enter, germs soon swarm within the lymph-vessels. This leads to an inflammation of the walls of the vessels, which may then be seen as red lines beneath the skin. These red lines lead upwards towards the nearest lymphatic gland. The glands in the space behind the knee are not usually affected when the focus of infection is in the foot. The red lines can be traced up the inner side of the knee and the front and inner side of the thigh to the groin. The glands in this situation swell until they can be easily felt. If the mischief is in the hand, the gland at the elbow may be affected, but most of the lymphatics pass by it on their course to the glands in the armpit. If a sore throat is the source of infection, the glands beneath the angle of the jaw enlarge. Thus various glands block the further progress of infection. In doing this their resources may be strained to the uttermost; they may enlarge, become tender, grow soft, fill with pus, break down and discharge the pus without the aid of a surgeon’s knife, although as soon as pus is recognizable within them it is wise to let it out. If germs pass through these first stations into the lymph-vessels beyond them, abscesses are formed in other situations. A condition of “blood-poisoning,” so called, is set up.

The readiness with which leucocytes sacrifice themselves in their efforts to remove germs and decaying tissue is a matter of almost every-day experience. The fatty matter produced in the sebaceous glands of the skin normally overflows on to the surface. It serves to render the skin supple and impervious to water. Germs get into one of the sebaceous glands of the face or of the eyelid. The contents of the gland begin to decompose. Leucocytes enter it for the purpose of removing the putrescent substance. They lose their vitality and turn into pus corpuscles. The pimple or the stye bursts, and pus and fatty matter are discharged together.

That the conversion of leucocytes into pus cells is due to want of oxygen has been shown by the following experiment: A minute piece of phosphorus is placed beneath the skin. Leucocytes gather round the spot with a view to removing the tissue which the phosphorus has destroyed. But phosphorus has so strong an affinity for oxygen that it exhausts the supply in the area of tissue which surrounds it. The leucocytes die before reaching the tissue immediately adjacent to the piece of phosphorus. Their dead bodies form round it a raised ring of pus cells. We can explain this readiness of leucocytes to sacrifice themselves in their efforts to reach foreign matter which needs to be removed, only by saying that the attraction of the food is greater than the repulsion of lymph destitute of oxygen. An amœba placed in comparable circumstances gives up the quest of food, however strongly chemiotaxic, and retreats towards water which contains oxygen sufficient to provide for its respiratory needs.

=Blood.=—A portion of the body fluid is enclosed within vessels and kept in circulation by the heart. The heart pumps blood into the aorta. This trunk gives off large arteries, which in turn divide until the finest capillary vessels are reached. The capillary tubes reunite to form veins, which, with the exception of those which collect food from the digestive organs, convey the blood right back to the heart. The veins which drain the stomach and intestines (the organs in which food is prepared for absorption) and the spleen (the organ in which worn-out red blood-corpuscles are in a sort digested) break up in the liver into a second set of small vessels. The pseudo-capillary vessels of the liver reunite to form the hepatic veins, which add the blood that has passed through that organ to the rest of the blood which is passing up the inferior vena cava to the heart. A second capillary circulation is found in the kidney also.

The heart is four-chambered (Fig. 10). Its left ventricle drives the blood round the systemic or greater circulation, the blood returning to the right auricle. The right ventricle drives the blood through the lesser or pulmonary circulation, from which it returns to the left auricle. The walls of all bloodvessels, except capillary tubes, are sufficiently thick to prevent the escape of any of the constituents of blood. To support the pressure of the blood which they contain, the arteries and the larger veins need walls of considerable thickness. The walls of the capillaries allow an interchange between blood and lymph in the manner already described (_cf._ p. 39).

Blood fresh from the lungs, whether still in the pulmonary veins or in the systemic arteries, is scarlet in colour. Venous blood is darker and purple-red, the depth of its tint varying with the extent to which it has parted with its oxygen. It looks less opaque than arterial blood. With this exception, the physical properties and chemical composition of blood are remarkably constant in all parts of the body. Arterial blood contains more oxygen, venous blood more carbonic acid. Other chemical differences can be recognized, but they are relatively very small. The constancy in the constitution of blood is its most notable character. Bleeding, unless excessive, does not greatly affect it. The number of corpuscles is of course diminished, but even these are replaced with great rapidity. The plasma, after bleeding, soon recovers its proteins and salts. A similar readjustment occurs if normal saline solution (water containing 0·9 per cent. sodic chloride), or even a strong solution of salt, is injected into the blood. Within certain limits it is very difficult to disturb the balance of its constituents. It gets rid of substances added in excess, or replaces substances removed, with remarkable facility. If sugar (glucose) be injected into a vein, it escapes through the capillary walls into the lymph. After a short interval the lymph contains more sugar than the blood. If an excess of protein, whether of a kind foreign to the blood or its own serum-albumin, be injected, it is removed by the kidneys. The blood has various sources from which it can draw out reserves of anything that is lacking, and various ways of getting rid of anything that is in excess. It draws upon the lymph in the tissue-spaces for water. It discharges salts into the lymph. It also takes salts from the lymph. It draws upon the liver for sugar, and probably for proteins also. In a starving animal the blood still contains sugar long after fresh supplies have ceased to reach it from the intestines. The lungs remove its carbonic acid. The kidneys free it from everything which cannot be otherwise removed. It is essential to the well-being of the organism as a whole that a uniform standard of composition should be maintained by the blood.

_Composition._—The structural composition of the blood, and the relation of its several constituents to each other, is best studied under the microscope. A thin transparent membrane in which blood is circulating through small vessels—the web between the toes of a frog’s foot, the mesentery, the membrane of a bat’s ear—affords an opportunity of observing blood in circulation. In any of the smaller vessels, whether artery or vein, a column of red corpuscles is seen moving in the axis of the stream. This column is surrounded by a layer of clear plasma. Amongst the red corpuscles a few leucocytes may be detected floating placidly down the current. Others are seen in the peripheral layer of plasma, tending to creep along the wall of the vessel rather than submit to be moved forward, as passive objects, by the current. If an irritant be applied to the membrane, the vessels dilate; yet, notwithstanding their wider calibre, the current becomes slower. The red corpuscles mass together. Apparently their constitution is slightly altered by this commencing inflammation, in such a manner that they cease to be clean, independent discs which slide past each other like small boats on a river; they exhibit a tendency to stick one to another. In the capillary vessels leucocytes may now be observed, not merely creeping along the inner surface of the endothelium, but squeezing themselves between its scales; making their way out of the vessel into the tissue-spaces through which the vessel passes. Such an observation gives the clue to the functions of the several constituents of the blood. The red corpuscles carry oxygen in chemical combination with their colouring matter. From them it passes into solution in the plasma; from the plasma through the walls of the capillary vessels into lymph; the tissues take it from the lymph as they require it. As fast as it is removed from lymph it is renewed from plasma. Carbonic acid excreted by tissue cells is dissolved in lymph. From lymph it is transferred to plasma. The reception of carbonic acid by these fluids is not quite so simple as the transference of oxygen from blood to lymph. It is aided by the presence of alkaline carbonates which are always ready to form “acid” salts: not acid to litmus-paper—the blood is always alkaline—but containing more than one unit of acid to one of base. Sodic carbonate has the formula Na₂CO₃. With an additional molecule of carbonic acid it becomes Na₂CO₃CO₂(HO)—bicarbonate. When in solution it can hold still more carbonic acid. If carbonic acid were merely dissolved in lymph and plasma, it would be impossible for the blood to carry it away with sufficient rapidity; just as it would be impossible for blood to bring sufficient oxygen were it not for the colouring matter (hæmoglobin) which forms a temporary, easily divorced union with it. But from a physical point of view it comes to the same thing. As the tension of oxygen in plasma falls, it dissolves more from the hæmoglobin. When the tension of oxygen in lymph is less than its tension in plasma, the former borrows from the latter. If the tension of carbonic acid in lymph is higher than in blood, it passes to the blood. The rapidly circulating blood at frequent intervals traverses the lungs. The whole blood of the body is exposed to air in the lungs once every minute. Oxygen tension being higher in pulmonary air than in venous blood, this gas is taken up. Carbonic acid tension being higher in venous blood than in pulmonary air, this gas escapes. The plasma in the capillary vessels which traverse the tissues exchanges gases with the lymph with very great rapidity.

The specific gravity of blood varies from 1·056 to 1·059. The corpuscles are heavier than the plasma. Its reaction to test-paper is alkaline, owing to the presence of bicarbonate of soda and disodic phosphate. The alkalinity is greatest when the body is at rest; it is diminished by severe muscular exercise. Blood contains about 5,000,000 red corpuscles, and 7,000 or 8,000 leucocytes, to a cubic millimetre. Red blood-corpuscles are biconcave discs destitute of nucleus, and, so far as can be seen, devoid of any investing membrane. Seen in profile they appear biscuit-shaped, because the centre is hollowed out. Their largest diameter is 7·5 micromillimetres (¹/₃₂₀₀ inch)—a measurement of great importance to anyone who works with a microscope, because it serves as a standard by which to estimate the size of other objects. They are soft, but fairly tough and highly elastic. In circulating blood a corpuscle may occasionally be seen to catch on the point where two capillary vessels unite. It bends almost double under the pressure of the column of corpuscles behind it, and then springs forward.

A red corpuscle is a vehicle for hæmoglobin. If blood is diluted with water, or if it is alternately frozen and thawed, the hæmoglobin separates from the corpuscles, which can then be seen as colourless discs. Hæmoglobin constitutes 40 per cent. of the weight of a moist corpuscle, or 95 per cent. of its weight after it has been dried. This is an enormous charge for a corpuscle to carry, and the question of how it carries it has been much discussed. It is not in a crystalline state. A corpuscle examined by polarized light is not doubly refractive. Microscopists know that if there were any crystals in the corpuscle it would appear bright on a dark ground when the Nicholl prisms are crossed. It cannot be in solution, since the water which the corpuscle contains would not suffice to dissolve it. It must be combined with some constituent of the corpuscle. But whether it is uniformly distributed throughout the disc, or in a semifluid form enclosed in spaces in a sponge-work; or whether the corpuscle is a hollow vesicle enclosing fluid hæmoglobin—a view which was long ago maintained, and has recently been revived—are questions which still await further evidence.

Red blood-corpuscles, properly so called, are found only in vertebrate animals, although invertebrate animals, from worms upwards, possess genuine blood, and in some of them it contains hæmoglobin, or a similar pigment in the form of globules. These might be likened to the non-nucleated corpuscles of mammals, but it must be remembered that the non-nucleated cells of mammals have been evolved from the nucleated blood-corpuscles of birds, reptiles, amphibians, and fishes. Below fishes red blood-cells are not found. Hæmoglobin is usually dissolved in the blood of invertebrate animals. It is impossible to trace any relationship between the coloured globules of invertebrates and the blood-cells of fishes. The coloured globules must be regarded as deposits or accretions of hæmoglobin held together by a proteid substance.

The nucleated red corpuscles of submammalian vertebrates multiply by cell division while circulating in the blood-stream. A good subject in which to look for dividing corpuscles is the blood of a newt in spring-time, when rapidly increasing activity calls for an additional supply. There is nothing to distinguish the method of division of a nucleated blood-corpuscle from that of any other cell.

The life-story of the red blood-corpuscles of mammals is one of the most fascinating that the histologist has to tell. He wishes that he could tell it with assurance; but, unfortunately, there are many uncertainties, due to conflicting testimony, in its earlier chapters. It is unlikely that a blood-corpuscle lives for long. A month or six weeks is probably the term of its existence. The rapidity with which the stock is replenished after bleeding shows that there must be ample provision in the body for making blood-corpuscles. The rate at which they disappear after they have been added in excess shows that there is an equally effective mechanism for destroying them. If half as many again as the animal already possesses be injected into its veins, the number is reduced to its normal limit in about ten days. It is clear that they can be made and can be destroyed with great facility, and it seems a legitimate inference that production and destruction are constantly taking place. Regarding the way in which they are destroyed there is no uncertainty. We shall refer to this subject when describing the functions of the spleen. But how are they made? We can sketch their history in outline, but the evidence is conflicting with regard to all matters of detail.

In early stages of embryonic life all red blood-corpuscles are nucleated, as they are permanently in birds and the other classes of vertebrates below mammals. In embryonic mammals they multiply by division whilst circulating in the blood, just as in the newt. But it is generally believed that this is not the most important source of new ones. During the earliest stages of growth they are being formed in enormous numbers. Such instances of division as can be seen in circulating blood appear to be all too infrequent to account for their rapid multiplication, and there can be no doubt but that a more complicated method of production is more important. Their formation is described as taking place “endogenously.” Certain cells termed “vaso-formative,” or “vaso-sanguiformative,” reach a considerable size, and become stellate in form, or branched. Their nuclei divide without the cell dividing. Each nucleus accumulates a little hæmoglobin round it. A space filled with fluid appears inside the cell. The nuclei project into this space. Then they drop off with their envelopes of hæmoglobin. The outer shell of the big vaso-formative cell becomes the wall of a capillary bloodvessel. By its branches it links up with other vaso-formative cells, making a network of vessels. The fluid inside it is the plasma of the blood. The nuclei and their envelopes are blood-corpuscles. This, if it be a true story, is a comprehensive way of making bloodvessels and blood at the same time. Doubts have been thrown upon its accuracy, but many leading histologists strenuously maintain that this description is correct.

At a certain period all nucleated red corpuscles disappear from mammalian blood. Non-nucleated corpuscles take their place. How are the latter formed? For a short stage of embryonic life nucleated cells containing blood-pigment are seen, or are supposed to be seen, in the liver—there is, unfortunately, great difficulty in distinguishing them with certainty from young liver-cells; later they are seen in the spleen; throughout the whole of life they are to be seen in the marrow of bone. The nucleated cells give origin to the non-nucleated corpuscles. It is hardly legitimate to call these cells persistent embryonic corpuscles. Yet the chain which connects the cells which in the embryo are capable of dividing into pairs of nucleated red blood-corpuscles, and the cells which, assuming the rôle of parent cells, do not accumulate hæmoglobin for their own purposes, but for the benefit of the red corpuscles which split off from them, is probably unbroken. In this sense they are persistent embryonic corpuscles which have deserted the blood-stream, and have taken shelter in certain tissues which are particularly favourable for cell division. The situations in which they hide themselves are singularly suggestive. In the liver there is an abundant supply of nutriment, more abundant than in any other part of the body of the embryo. Later, in the spleen, red blood-corpuscles are being destroyed. Materials available for making new ones must therefore be set free. The inside of a hollow bone is a peculiarly sheltered situation. The fat cells of marrow accumulate there after a time; but within some bones the marrow develops very little fat; hence it shows the red colour, which is due to its abundant bloodvessels. This “red marrow” is the most important seat of the manufacture of red blood-corpuscles in adult life. Unfortunately, when we try to answer the question, How are they formed? we are obliged to speak with caution. Some histologists assert that the nucleated cells divide, and that one of the two daughter cells accumulates hæmoglobin, and loses—that is to say, extrudes—its nucleus. Others maintain that the nucleated cells become irregular in form; that hæmoglobin accumulates in the projecting portion of the cell; that this projecting portion breaks off as a non-nucleated corpuscle. It would be indiscreet at the present time to pronounce in favour of either of these reports, although the decision is of theoretical importance. If the former account be true, red blood-corpuscles are nucleated blood-cells which have lost their nuclei. If the latter account be in accordance with fact, it is hardly justifiable to regard them as cells. They are parts of cells which finish their existence independently of the cell body and nucleus to which they belong. As circumstantial evidence, favouring the theory that cell division is normal and the nucleus subsequently lost, may be pleaded the existence in marrow, and also in the embryonic liver and spleen, of certain very peculiar cells. These cells have long been known as giant cells, and all attempts at accounting for them have broken down. They are relatively of immense size: their diameter may be twenty times as great as that of a red blood-corpuscle. Each contains a huge irregular, bulging nucleus. Hence the cells are termed “megacaryocytes” (big-nucleus cells). They must not be confounded with the polycaryocytes (cells with several nuclei), which eat up degrading bone, although it must be confessed that megacaryocytes and polycaryocytes appear to be genetically connected. It is supposed that megacaryocytes consume the nuclei which red corpuscles extrude during the process of their conversion from nucleated cells. Traces of nuclei, or things which often look like nuclei, are found in their body-substance. Their own overgrown misformed nuclei appear to be the result of an excess of nuclear food. It is certainly remarkable that megacaryocytes are not found below mammals. They do not occur in any animal in which red blood-corpuscles retain their nuclei. Polycaryocytes are found in numbers in the bones of growing birds. They are evidently scooping out bone from situations in which it has to be displaced in order that the shape of the bone as a whole may be changed. But there are no megacaryocytes in birds. On the other hand, megacaryocytes are present in the liver, and later in the spleen, of mammals at the periods when blood-formation is occurring most actively in these organs. From the liver they disappear early. In most mammals they disappear from the spleen about the time of birth; but in some—the hedgehog, for example—they are found in the spleen throughout the whole of life.

Hæmoglobin is a substance which has the property of uniting with oxygen to form oxyhæmoglobin—a compound from which the oxygen is, again, very readily withdrawn. It is extremely soluble, but may be made to crystallize by adding alcohol to blood, after setting the hæmoglobin free from the corpuscles by freezing and thawing. From the blood of Man and most other animals it crystallizes in the form of rhombic prisms, whether in the oxidized (oxyhæmoglobin) or non-oxidized condition. The addition of oxygen does not affect its crystalline form; although crystalline, it is absolutely non-diffusible. This is due to the great size of its molecule, which is probably larger than that of any other substance which is capable of crystallizing.

The percentage composition of hæmoglobin conforms closely with that of albumin and other proteins, with this most important difference: it contains a definite proportion of iron—0·336 per cent. That the percentage of carbon, hydrogen, nitrogen, sulphur, and oxygen should agree with that commonly found in proteins is inevitable, since it may be split into a part which contains all the iron, hæmatin, and a proteid part resembling albumin; and the latter constitutes 96 per cent. of its weight.

There is no doubt but that its value as a vehicle of oxygen depends upon the presence of iron. In the matter of taking up and dropping oxygen, hæmatin behaves somewhat in the same manner as hæmoglobin; whereas if iron be removed from hæmatin the “iron-free hæmatin” loses its respiratory value. It is almost certain that a molecule of hæmoglobin contains a single atom of iron. On this supposition its molecular formula may be calculated. It is not quite the same for all animals, although the variations are slight. For the blood of the horse it is as follows:

C₇₁₂H₁₁₃₀N₂₁₄S₂FeO₂₄₅.

This means a molecular weight of 16708. We give the figures, because the properties of hæmoglobin will be better understood if its prodigious molecular weight is borne in mind. In a sense, the reason for the great size of its molecule is not far to seek. The atomic weight of iron (Fe = 56) is much greater than that of either of the other elements contained in hæmoglobin. The molecule needs to be very great to float an atom of iron. As it is, the corpuscles are heavier than the plasma which surrounds them, in the proportion of about 13 to 12. Although hæmoglobin is a crystallizable substance, its immense molecule is absolutely non-diffusible. It cannot pass through a membrane. This is of no consequence as regards the relation of hæmoglobin to the walls of the capillary bloodvessels, since it is contained in corpuscles; but it is of great importance as regards its relation to the discs which carry it. A very small quantity of enveloping substance suffices to prevent it from diffusing into the plasma of the blood. The great molecules are held together and isolated from the fluid in which they float by a minimal amount of insoluble globin.

The iron needed for the making of hæmoglobin is obtained both from meat and vegetables. The constituents of an ordinary diet provide from 2 to 3 centigrammes of iron a day. The whole of the blood contains about 4·5 grammes. When corpuscles are being destroyed in the spleen, the iron which their pigment contains is largely reabsorbed and rendered available for further use. The iron in a mixed diet is more than sufficient to counterbalance any loss. Milk contains extremely little iron. Before birth the liver and spleen accumulate a store of iron which lasts until the end of the nursing period, unless this be unduly prolonged. If it be prolonged, the child is apt to become anæmic. Iron has been administered in the treatment of anæmia ever since its presence in the red clot of blood was recognized a hundred and fifty years ago. Physicians are agreed that in the anæmia of young people it is of value; but observations made with a view to obtaining definite data as to the increase in number of blood-corpuscles which results from the administration of iron, without any other alteration in the diet or the habits of the patient, have not given accordant results. Some observers have obtained an increase with organic compounds of iron, others with inorganic compounds; some are in favour of small doses, others of very large ones. As in the treatment by drugs of other abnormal conditions, it is difficult to isolate the effect of the drug from the effects of improvements in the general regimen. Yet physicians agree that iron accentuates the beneficial effects of fresh air and improved diet.

When the surface of the body is struck, the effect of the blow is marked at first by redness. There is nothing to show that small bloodvessels have been ruptured and blood effused beneath the skin. Next day the injured area is reddish-purple. The bruise turns blue, green, yellow, and eventually disappears. In the process of absorption, oxyhæmoglobin undergoes decomposition. First its proteid constituent is removed, leaving a coloured pigment containing iron, termed “hæmatin”; soon reduced by loss of oxygen to hæmochromogen. When Sir George Stokes first described the spectrum of blood (_cf._ p. 185), he showed that as hæmoglobin may exist in an oxidized and in a non-oxidized condition, distinguished by their spectra, so also may the coloured residue which is left after the proteid constituent has been removed from hæmoglobin. This coloured residue he termed, when oxidized, “hæmatin”; when not oxidized, “reduced hæmatin.” Stokes’s reduced hæmatin is now termed “hæmochromogen.” Hæmochromogen stands for the coloured nucleus of hæmoglobin. Although it is not present in hæmoglobin as hæmochromogen—hence we must not speak of hæmoglobin as made of a protein, _x_, plus hæmochromogen, _y_—it is to its coloured residue that hæmoglobin owes its value as a carrier of oxygen. Later, iron is removed from hæmochromogen, leaving hæmatoidin, a substance often found at the seat of old hæmorrhages, where it may remain unchanged for a very long time. Hæmatoidin is apparently identical with the yellow pigment of bile, bilirubin. The green colour which shows itself in the bruise seems to indicate that the more oxidized bile-pigment, biliverdin, is formed in the first instance. Red corpuscles, when destroyed in the spleen, pass through transformations similar to those which blood undergoes when effused beneath the skin. Their protein is used by the phagocytes which eat them. Their iron is reserved for the use of the blood-forming cells of the red marrow of bone. The pigment which remains as the residue of hæmoglobin is carried by the splenic vein to the liver, which secretes it as bile-pigment. So much of the bile-pigment as is reabsorbed by the wall of the alimentary canal is eventually excreted as the pigment of urine.

Such is the history of the changes which blood-pigment undergoes within the living body. To a certain extent its chemistry can be followed in the laboratory; but it must be remembered, when we are treating of the chemistry of a substance as complex as hæmoglobin, that the products which can be obtained from it in the laboratory are not necessarily those into which it is transformed in the body. In the laboratory oxyhæmoglobin is easily changed into methæmoglobin, a substance of the same percentage composition, but with its oxygen more firmly fixed. Methæmoglobin can be decomposed into a proteid substance and hæmatin. Hæmatin, when acted on by reducing agents, becomes hæmochromogen. Hæmochromogen, when subjected to such a reducing agent as a mixture of tin and hydrochloric acid, gives rise to coloured bodies closely resembling bile-pigments—not as they are secreted by the bile, but as they appear in the urine. It is impossible to prove that the changing colours of a bruise indicate a sequence of chemical transformations from hæmoglobin to bile-pigment, but it is not improbable that such a description is correct. The test commonly used to ascertain the presence of bile-pigment, _i.e._, bilirubin, is the play of colours which it exhibits when oxidized by fuming nitric acid. From yellow it turns to green, to blue, and then to purple, more or less reversing the colours of the bruise. It is fairly certain that effused blood undergoes changes along lines which, if not identical with those through which blood passes on its road to bile-pigment, are at any rate very similar.

=Coagulation of Lymph and Blood.=—Two or three minutes after blood has been shed it begins to clot. In ten minutes the vessel into which it has been received may be inverted without spilling the blood. After a time the jelly, holding all the corpuscles, shrinks from the sides of the jar. It squeezes out a transparent, straw-coloured fluid—serum. The clot continues to contract until, in a few hours, about one-half of the weight of the blood is clot, the other half serum. Lymph coagulates like blood, but most specimens clot more slowly, and the product is less firm.

When the process is watched through the microscope—a few drops of the almost colourless, transparent blood of a lobster afford an excellent opportunity of studying the formation of the clot—innumerable filaments of the most delicate description are seen to shoot out from many centres. They multiply until they constitute a felt-work. In the case of blood obtained from a vertebrate animal, this felt-work holds the corpuscles in its meshes. Its filaments exhibit a remarkable tendency to contract. They shorten as much as the enclosed corpuscles allow.

The filaments may be prevented from entangling the corpuscles by whipping the blood, from the instant that it is shed, with a bundle of twigs or wires. The fibrin collects on the wires, while the corpuscles remain in the serum. If this fibrin is washed in running water until all adherent serum and corpuscles are removed, it appears as a soft white stringy substance which, when dried, resembles isinglass.

Clotting is a protection against hæmorrhage. As it oozes from a scratch or tiny wound, blood clots, forming a natural plaster which prevents continued bleeding. It has little if any influence in resisting a strongly flowing stream of blood. But a clean cut through a large vessel is an accident which rarely happens as the result of natural causes. It is not the kind of injury to which animals are liable. When an artery is severed by a blunt instrument, the muscle-fibres of its wall contract. They occlude the vessel. The blood clots at the place where the vessel is injured, and plugs it. This happens also when a surgeon ties an artery. He is careful to pull the ligature sufficiently tight to crush its wall. His sensitive fingers feel it give. He stops before the thread has cut it through. As will be explained later, the clotting of blood is promoted by contact with injured tissue. If in tying an artery its wall be not crushed, the blood in it may remain liquid. When it is skilfully tied, the blood clots, forming a firm plug which is practically a part of the artery, by the time that the silk thread used in tying it is thrown out, owing to the death of the ring of tissue which it compressed. After a tooth has been extracted, the cavity is closed and further bleeding stopped by clotted blood.

When large vessels have been severed, the copious hæmorrhage which follows induces fainting. For a short time the heart stops, or beats very feebly. The blood-pressure falls. The bloodvessels contract. A clot has time to form. An emotional tendency to faint at the sight of blood is a provision for giving the various causes which stop bleeding an opportunity of coming into play. It is a useful reflex action, always supposing that the person who is liable to it faints at the sight of his own blood. Amongst other reasons for the greater fortitude of women—they are far less subject to this emotional reflex than men—might be alleged the circumstances of life of primitive people. It was the part of their women-folk to dress wounds, not to receive them.

The phenomenon of coagulation has attracted attention from the earliest times. It was a phenomenon that needed explanation, and culinary experience suggested analogies close at hand. Hippocrates attributed the clotting of blood to its coming to rest and growing cold. The blood which gushed from a warrior’s wound formed a still pool by his side. It set into a jelly as it cooled. Until the second quarter of the nineteenth century this theory was deemed sufficient. It then occurred to two men of inquiring mind to institute control experiments. John Davy placed a dish of blood upon the hob. William Hunter kept one shaking. In both experiments the blood clotted more quickly than it did in vessels of the same size, containing the same amount of the same blood, left upon the table.

Even before this date an observation had been made regarding the circumstances in which clotting occurs, which has thrown much light upon the causes of the phenomenon. In 1772 Hewson gently tied a vein in two places. At the end of a couple of hours he opened the vein. The blood was still liquid, but clotted in a normal manner after it was shed. Scudamore showed that blood clots more slowly in a closed than in an open flask. A new theory, as little trustworthy as Hippocrates’, was based upon these observations. Blood clotted because it was exposed to air. A record of all observations of the circumstances of coagulation, and of all the theories to which they have given rise, would make an exceptionally interesting chapter in the history of human thought. It would bring into singular prominence stages in the development of what is now known as the “scientific method.” Not that Science has a method of her own. Philosophers of all classes would follow the same method if their data allowed of its application. The peculiarity of the data with which Science deals is that they can be brought to a test of which the data of historical, or political, or economic theory are not susceptible. They can be confronted with control experiments. The control experiment is the alphabet and the syntax of the scientific method. No hypothesis is admissible into the pyramid of theory until it has passed this test. A natural phenomenon is observed. Every measurement which is applicable is taken and recorded—time, weight, temperature, colour. Scientific observation implies the tabulation of all particulars which are capable of statistical expression. Reflecting upon the relation of the phenomenon to other phenomena of a like nature, the philosopher—it is the philosophy of physiologists which interests us—formulates an hypothesis as to its cause. At this point the real difficulty of applying the scientific method begins. It is easy to formulate hypotheses. It is very difficult to devise control experiments. An experiment must be arranged which will provide that, while all other conditions in which the phenomenon has been observed to occur are reproduced, the condition which was _ex hypothesi_ its cause shall be omitted. This digression into the philosophy of science may seem to be somewhat remote from our line of march, but it may perhaps hasten our progress in the comprehension of the story of physiology. There is no other science in which the control experiment plays an equally important part. Unless this is realized, the whole trend of experimental work will be misunderstood. Scudamore explained coagulation as due to contact with air. Based on the observations we have cited, no hypothesis could have seemed more reasonable. With a view to checking this hypothesis, blood was received into a tube of mercury. It coagulated in the Torricellian vacuum. Scudamore’s hypothesis, like many earlier and later, when confronted with a control experiment, was turned away, ashamed.

Clotting is a property of plasma. Red corpuscles play no part in the process. Coagulation does not occur in a living healthy vessel. It occurs when the vessel, and especially when its inner coat, is injured. It is hastened by contact with wounded tissues, especially with wounded skin. Contact with a foreign body also starts coagulation. If a silk thread is drawn through a bloodvessel, from side to side, fibrin filaments shoot out from the thread, as well as from the wound inflicted on the vessel by the needle which was used to draw it through.

Plasma contains a substance which sets into fibrin. It has been termed “fibrinogen.” It is present in lymph, and in almost all forms of exuded lymph. If sodium chloride (common salt) is added to plasma until it is half saturated—until it has dissolved half as much as the maximum quantity which it can dissolve—fibrinogen is thrown down as a flocculent precipitate. It can be redissolved and reprecipitated until it is pure. When fibrinogen was separated from plasma a step was taken towards the explanation of coagulation. Under certain conditions fibrinogen sets into fibrin. The question which then presented itself for solution was as follows: What is the substance which, by acting upon or combining with fibrinogen, converts it into fibrin? The clue to the solution of this question was obtained from the consideration of certain observations made by Andrew Buchanan in 1830, but long neglected, because their significance was not understood. Buchanan had observed that some specimens of lymph exuded into a lymph-space—the peritoneal cavity, for example—will clot; others will not. He noticed that they clot when, owing to puncture of a small bloodvessel during the process of drawing them off, they are tinged with blood. Determined to ascertain which of the constituents of blood is effective in rendering non-coagulable effusions capable of clotting, he added to them in turn red blood-corpuscles, serum, and the washings of blood clot. Either of the two latter was found to contain the clot-provoking substance. Thirty years later a German physiologist prepared fibrinogen from effused lymph by precipitating it with salt. He also treated serum in a similar way, precipitating a protein which he termed fibrinoplastin. When these two substances were dissolved and the solutions mixed, he obtained a clot, which he regarded as a compound of fibrinogen and fibrinoplastin. Subsequently he found that the mixture did not always clot, but he discovered that if he coagulated blood with alcohol, and washed this residue, the washings added to the mixed solution just referred to invariably produced a clot. Thinking that the substance which he obtained from his alcohol-coagulated blood could not be proteid, he termed it “fibrin-ferment.” He neglected the control experiment. He failed to ascertain whether or not all three substances were needed. Had he tried adding fibrin-ferment to fibrinogen, he would have discovered that the further addition of fibrinoplastin was unnecessary. He did not ascertain, as he might have done, that the weight of fibrin formed is somewhat less, not greater, than the weight of fibrinogen used. (Fibrinogen gives off a certain quantity of globulin when it changes into fibrin.) He was also wrong in supposing that the water which he added to alcohol-coagulated blood dissolved no protein. His “fibrin-ferment” is always associated with a protein. Since it may also be obtained from lymphatic glands, thymus gland, and other tissues which contain lymphocytes, it has been inferred that it is itself a protein, of the class known as nucleo-proteins. The fact that it is destroyed at so low a temperature as 55° C. has been supposed to confirm the theory that it is a protein. But with regard to the chemical nature of fibrin-ferment, as of all other ferments, we are at present in the dark. Under ordinary circumstances, when blood clots, the fibrin-ferment, or plasmase, or thrombin—it has received various names—is set free by leucocytes. Fluids which contain fibrinogen clot on the addition of a “ferment” which is either secreted by leucocytes or set free from leucocytes when they break up—as they are very apt to do, as soon as the conditions upon which their health depends are interfered with.

Freshly shed blood contains minute particles, termed “platelets,” in diameter measuring about a quarter that of a red blood-corpuscle. When the inner coat of a vessel is injured, platelets accumulate at the injured spot. They form a little white heap, from which coagulation starts. Evidently they supply the ferment, or a precursor of the ferment. As yet their origin has not been traced. They are too large to be the unchanged granules of granular leucocytes, but that they are in some way derived from leucocytes seems probable.

The further study of coagulation has shown that the conditions under which it occurs are more complicated than the simple explanation just given would seem to imply. This explanation holds good, so far as it goes, but facts connected with the details of the process have recently been brought to light which warn the physiologist that as yet his theory of coagulation is incomplete.

The presence of salts of lime has an important relation to coagulation. If blood is received into a vessel in which has been placed some powdered oxalate of potash, or soap, or any other chemical which fixes lime, the blood does not coagulate. All other conditions are as usual, but lime is withdrawn from the plasma. The non-coagulation of oxalated plasma was interpreted as indicating that lime, under the influence of fibrin-ferment, combines with fibrinogen to form fibrin; that fibrinogen altered by fibrin-ferment combines with lime. This hypothesis was based upon the analogy of the curdling of milk. Milk cannot curdle if lime be absent. If rennin (milk-ferment), prepared from milk from which lime has been removed, be added to a solution of caseinogen (the coagulable protein of milk), also prepared from lime-free milk, no curd is produced. The addition of a few drops of a solution of chloride of lime results in the immediate curdling of the mixture. Evidently rennin so alters caseinogen as to bring it into a condition to combine with lime. But the analogy does not hold good for blood. In the case of plasma, lime acts, not upon fibrinogen, but upon the fibrin-ferment—or rather upon a precursor of fibrin-ferment—in such a way as to render it effective. Leucocytes produce a prothrombin, which in contact with lime salts is converted into thrombin, which coagulates fibrinogen.

Fibrinogen is the substance which fibrin-ferment combined with salts of lime changes into fibrin. Yet even now the story is not complete, if the theory of coagulation is to be brought up to date. A perfectly clean cannula is passed into an artery of a bird. If it be thrust well beyond the place where the vessel has been cut, if the vessel be tied so gently as to avoid injury to its inner coat, and if the blood which first passes through the cannula be allowed to escape, the blood subsequently collected will not clot. It contains fibrinogen, lime salts, and fibrin-ferment, ordinarily so called; but the ferment is ineffective. The addition to the blood of a fragment of injured tissue, or of a watery extract of almost any tissue, immediately sets up coagulation. This observation brings fibrin-ferment into line with other ferments. Digestive ferments are secreted as zymogens, which require to be influenced by a kinase before they acquire fermentative activity. So, too, must thrombogen be changed into thrombin, under the influence of thrombokinase, before it can act upon fibrinogen. Almost all tissues yield the kinase which actuates fibrin-ferment. The utility of this provision is manifest. A bird’s blood contains everything necessary to form a clot with the exception of thrombokinase. The injury which brings the blood into contact with a broken surface supplies this ferment of the ferment. Fibrin-ferment, rendered active, at once changes fibrinogen into fibrin. The same interaction is necessary before the blood of a mammal is susceptible of clotting. But a mammal’s blood is even readier to clot than is the blood of a bird; for not only will a broken surface provide it with thrombokinase, but the leucocytes contained within the blood, when injured, also yield it. And the leucocytes are exceedingly sensitive of any change of circumstance; on the slightest indication that conditions are not normal they set free, perhaps owing to their own disintegration, the kinase which turns thrombogen into thrombin.

There is a constitutional condition, fortunately rare, in which blood does not coagulate. A person subject to this abnormality is said to suffer from hæmophilia. It is alleged that this condition is due to deficiency of lime in the blood; and the deficiency of lime is said to be due to excess of phosphates. The subject suffers from phosphaturia. His kidneys get rid of the superabundance of phosphates by excreting them in combination with lime. If this explanation be correct, there is a chronic insufficiency of lime in the blood, because it is being constantly withdrawn in the process of removing phosphates.

The difficulty in the way of establishing a complete theory of the coagulation of blood increases when the phenomena of incoagulability are considered. Blood may be rendered incapable of clotting in a variety of ways. Leeches and other animals which suck blood have the capacity of rendering it incoagulable. If the heads are removed from a score of leeches, thrown into absolute alcohol, dried, ground in a pepper mill, extracted with normal saline solution, a dark turbid liquor is obtained. This liquor, after filtration and sterilization at a temperature of 120° C., injected into the veins of an animal, renders its blood incoagulable.

The preparation sold by druggists under the name “peptone,” when injected into the veins of a dog, renders its blood incoagulable. Commercial “peptone” is a mixture of many substances. Its anticoagulation-effect is not due to the peptone which it contains. It has been supposed to be due to imperfectly digested albumin and gelatin (proteoses), but products of bacteric fermentation (toxins and ptomaines) are more probably the active bodies. Not only is the peptonized blood of a dog incoagulable, but if this blood be injected into the veins of a rabbit (an animal upon which the direct injection of peptone has no effect), it diminishes the coagulability of the rabbit’s blood. If peptonized blood be mixed in a beaker with non-peptonized blood, it prevents the coagulation of the latter. There is little doubt but that the poison, whatever it may be, acts upon the leucocytes; and there are some reasons for thinking that the poison is not contained in the “peptone,” but is secreted by the liver of the animal into which the “peptone” has been injected.

A still more remarkable property in relation to coagulation must be assigned to leucocytes. The blood of a dog which has been rendered incoagulable by injection of peptone recovers its coagulability after a time. If a further injection of “peptone” be made, the animal is found to be immune. Injection of “peptone” no longer renders its blood incoagulable. In a similar manner the blood develops a power of resisting the action of agents which induce its coagulation whilst circulating in the vascular system. Nucleo-proteins contained in extracts of lymphatic glands and other organs when injected into the veins of living animals cause their blood to clot, provided they are injected in sufficient quantity. If they are injected in quantity less than sufficient to induce coagulation, they render the animal immune to their influence. A larger quantity given to an animal thus prepared fails to take effect. This brings the phenomena of coagulation and resistance to coagulation to the verge of chemistry. They extend into the domain in which pathology reigns. Tempting though it be to record other facts with regard to these phenomena which recent investigation has brought to light, it is probably judicious to leave the problem at the frontier. Across the frontier lies a fascinating land, rich with unimaginable possibilities for the human race. Settlement is rapidly proceeding in this country, which is charted, like other border-lands, with barbarous names: “antibodies,” “haptors,” “amboceptors,” “toxins,” “antitoxins,” and the like—finger-posts to hypotheses which show every sign of hasty and provisional construction. But certain facts stand out, in whatever way theory may, in the future, link them up. The virus of hydrophobia, modified by passing through a rabbit, develops in human beings, even when injected after they have been infected, the power of resisting hydrophobia. The serum of a horse which has acquired immunity to diphtheria aids the blood of a child, which has not had time to become immune, in destroying the germs of this disease. It is a contest between the blood and offensive bodies of all kinds which find entrance to it, whether living germs or poisons in solution; with victory always, in the long-run, on the side of the blood, provided its owner does not die in the meantime. And not only is the blood victorious in the struggle with any given invader, but having repulsed him, it retains for a long while a property which neutralizes all further attempts at aggression on his part. In the past, physicians have fought disease with such clumsy weapons as mercury, arsenic, and quinine. Now they anticipate disease. In mimic warfare with an attenuated virus the blood is trained to combat. Smallpox which has been passed through the body of a cow is suppressed by the blood’s native strength. The exercise develops skill to deal with the most virulent germs of the same kind. In cases in which physicians cannot anticipate disease in human beings, they train the blood of animals to meet it; and, keeping their serum in stock, they can, when the critical moment arrives, reinforce the fighting strength of the patient with this mercenary aid.

=The Spleen.=—The spleen is placed on the left side of the body, and rather towards the back. It rests between the stomach and the inner surface of the eighth, ninth, tenth, and eleventh ribs. It is quickly distinguished from other organs by its brown-purple colour, a sombre hue to which it owed its evil reputation with the humoralists. The liver’s yellow bile tinged man’s mental outlook, preventing him from seeing objects in their natural brightness; but the spleen made black bile, which, mounting to the brain, displayed its malign influence upon the action of that organ, as, or in, the worst of humours.

The spleen is invested with a capsule of no great toughness. Inside the capsule is “spleen-pulp.” When the fresh organ is cut across, it is seen that, although most of the pulp is of the colour of dark venous blood, it is mottled with light patches. In some animals—the cat, for example—these whitish patches are small round spots, regularly arranged at a certain distance from the capsule. The distinction into “red pulp” and “white pulp” marks a division into two kinds of tissue with entirely different functions. The white pulp is lymphoid tissue, lymph-follicles developed in the outer or connective-tissue coat of the branches of the splenic artery. Its function is to make lymphocytes, of which, for reasons which will shortly appear, the spleen needs an abundant supply. The constitution of the red pulp is entirely different, and peculiar to the spleen. The branches of the splenic artery divide in the usual way into smaller and still smaller twigs until the finest arterioles are reached; but these arterioles do not give rise to capillary vessels. At the point at which in any other organ their branches would attain the calibre of capillaries, the connective-tissue cells which make their walls scatter into a reticulum. They are no longer tiles with closely fitting, sinuous, dovetailed borders, but stellate cells with long delicate processes uniting to constitute a network. The blood which the arterioles bring to the pulp is not conducted by closed capillary vessels across the pulp to the commencing splenic veins. It falls into the general sponge-work. The venules commence exactly in the same way as the arterioles end. Stellate connective-tissue cells become flat tiles placed edge to edge. The endothelium of an arteriole might be likened to a column of men marching shoulder to shoulder, three or four abreast; the connective tissue of the pulp, to a crowd in an open place. The column breaks up into a crowd. On the other side the crowd falls into rank as the endothelium of veins. The capsule and the red pulp are largely composed of muscle-fibres. These relax and contract about once a minute. By their contraction the blood is squeezed out of the sponge.

If the spleen be enclosed in an air-tight box (an oncometer), from which a tube leads to a pressure-gauge—a drum covered with thin membrane on which the end of a lever rests, or a bent column of mercury on which it floats—the pressure-gauge shows the changes in volume of the spleen. The long end of the lever, which records the variations of pressure in the gauge, may be made to scratch a line on a soot-blackened surface of travelling paper. A record of the variations in volume of the organ, which can be studied at leisure, is thus obtained. It shows that the spleen is sensitive to every change of pressure in the splenic artery. Small notches on the tracing correspond to the beats of the heart. Larger curves record the changes of blood-pressure due to respiration. A long slow rise and fall marks the rhythmic dilation and contraction of the spleen itself.

One of the three large arteries into which the cœliac axis divides delivers blood to the spleen direct from the aorta. The splenic vein joins the portal vein shortly before it enters the liver. Thus the spleen is placed on a big vascular loop which directs blood, not long after it has left the heart, from the aorta, through the spleen, to the liver.

The peculiar construction of the splenic pulp which brings the blood more or less to rest within its sponge-work, and the transmission to the liver of the blood which leaves the spleen, indicate that it is an organ in which blood itself receives some kind of treatment. It is not passed through it, as it is through all other parts of the body, in closed pipes. The spleen is a reservoir, or a filter-bed, into which blood is received.

The red blood-corpuscles of mammals are cells without nuclei, and with little, if any, body-protoplasm. They are merely vehicles for carrying hæmoglobin. We should deny to them the status of cell, if it were possible to prescribe the limit at which a structural unit ceases to be entitled to rank as a cell. They are helpless creatures, incapable of renewing their substance or of making good any of the damage to which the vicissitudes of their ceaseless circulation render them peculiarly liable. It is impossible to say with any approach to accuracy how long they last, but probably their average duration is comparatively short. The spleen is a labyrinth of tissue-spaces through which at frequent intervals all red corpuscles float. If they are clean, firm, resilient, they pass through without interference. If obsolete they are broken up. In the recesses of the spleen-pulp, leucocytes overtake the laggards of the blood-fleet, attach their pseudopodia to them, draw them into their body-substance, digest them. The albuminous constituent of hæmoglobin they use, presumably, for their own nutrition. The iron-containing colouring matter they decompose, and excrete in two parts; the iron (perhaps combined with protein); the colouring matter, without iron, as the pigment, or an antecedent of the pigment, which the liver will excrete in bile. Hæmoglobin is undoubtedly the source of bilirubin, and general considerations lead to the conclusion that it is split into protein, iron, and iron-free pigment in the spleen; but the details of this process have never been checked by chemical analysis. Neither bile-pigment nor an iron compound can be detected in the blood of the splenic vein. The only evidence of the setting free of iron in the spleen is to be found in the fact that the spleen yields on analysis an exceptionally large quantity of this metal (the liver also yields iron), and that the quantity is greatest when red corpuscles are being rapidly destroyed.

As a rule, it is very difficult to detect leucocytes in the act of eating red corpuscles; but under various circumstances their activity in this respect may be stimulated to such a degree as to show them, in a microscopic preparation, busily engaged in this operation. The writer had the good fortune to prepare a spleen which proved to be peculiarly suitable for this observation (Fig. 5). His method was an example of the way in which a physiological experiment ought not to be conducted. Having placed a cannula in the aorta of a rabbit, just killed with chloroform, he was proceeding to wash the blood out of its bloodvessels with a stream of warm normal saline solution, when the bottle from which the salt-solution was flowing overturned. Fearing lest an air-bubble should enter the cannula, he hastily poured warm water into the pressure-bottle, and threw in some salt, in the hope that it would make a solution of about 0·9 per cent. The salt-solution was allowed to run through the bloodvessel for rather more than an hour. When sections of the spleen were cut, after suitable hardening, every section was found to be packed with leucocytes gorged with red corpuscles. Some of the corpuscles had just been ingested; from others the hæmoglobin had already been removed. It may be that, for some unknown reason, the destruction of red corpuscles was occurring in this particular rabbit with unusual rapidity at the time when it was killed; but it seems more probable that the animal’s leucocytes were provoked to excessive activity by changes in the red corpuscles brought about by salt-solution which was either more or less than “toxic.” As a score of attempts to reproduce the experiment, with solutions of different strengths, have failed, it is impossible to be sure that this is a valid explanation.

There must be something in the condition of worn-out red corpuscles which either makes them peculiarly attractive to predatory leucocytes or renders them an exceptionally easy prey. It does not require much imagination to picture the drama which is enacted in the spleen. Slow-moving leucocytes are feeling for their food. The majority of red corpuscles pass by them; a few are held back. The leucocytes, like children in a cake-shop, cannot consume all the buns. A selection must be made, and preference is given to the sticky, sugary ones. Red corpuscles when out of order show a tendency to stick together. When blood is stagnating in a vein, or lying on a glass slide in a layer thin enough for microscopic examination, its red discs are seen after a time to adhere together in rouleaux. The parable of a child in a cake-shop is not so fanciful as it may appear.

The differentiation of function of organs is not as sharp as was formerly supposed. Evidence of their interdependence is rapidly accumulating. The activity of various organs is known to result in the formation of by-products termed “internal secretions,” which influence the activity of other organs, or even of the body as a whole. The spleen enlarges after meals. This may be merely connected with the engorgement of the abdominal viscera which occurs during active digestion, or it may indicate, as some physiologists hold, that an internal secretion of the spleen aids the pancreas in preparing its ferments. The spleen enlarges greatly in ague and in some other diseases of microbial origin. This has been regarded as evidence that it takes some part in protecting the body against microbes. But whatever may be the accessory functions which it exercises, they are not of material importance to the organism as a whole, seeing that removal of the spleen causes no permanent inconvenience either to men or animals. Its blood-destroying functions are taken on by accessory spleens, if there be any, and by lymphatic glands. The marrow of bone also becomes redder and more active. Under certain circumstances, red corpuscles, or fragments of red corpuscles, are to be seen within liver-cells; but it is uncertain whether blood-destruction is a standing function of the liver.